Lumacaftor/ivacaftor improves liver cholesterol metabolism but does not influence hypocholesterolemia in patients with cystic fibrosis

BackgroundCystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508).MethodsCholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin.ResultsBefore the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced.ConclusionsThese data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.     

Aggressive Intraosseous Myofibroma of the Maxilla: Report of a Rare Case and Literature Review

Myofibroma (MF) is a benign mesenchymal myofibroblast-derived tumor, which occurs most frequently in children, and rarely affects the maxilla. We reported a case of an aggressive intraosseous lesion found in the maxilla of a 9-year-old female child. Intraorally, the swelling extended from tooth 12 to 16, causing displacement of teeth 13, 14, and 15. Computed tomography revealed a large osteolytic lesion causing thinning and cortical erosion. Microscopically, the lesion showed a proliferation of spindle-shaped cells, with elongated nuclei and eosinophilic cytoplasm, arranged in interlaced fascicles. The immunohistochemical analysis revealed cytoplasmic positivity for α-SMA and HHF-35, and negativity for desmin, laminin, S-100, β-catenin, and CD34. Ki-67 was positive in 8% of tumor cells. The diagnosis was MF. Herein, we describe an additional case of central MF arising in the maxilla, including clinical, imaging, microscopical, and immunohistochemical features, as well as a review of the literature.     

COVID-19 pandemic reduces the negative perception of oral health-related quality of life in adolescents

Quality of Life Research - As people around the world are facing the Covid-19 outbreak, their perception of oral health problems could be changed. This study aimed to evaluate the immediate effects...     

Association between food patterns and difficulties in falling asleep among adolescents in Norway — a descriptive Young-Hunt3 study

Journal of Public Health - Adolescents’ sleep duration has decreased over the past century; this is mainly caused by problems with falling asleep. Short sleep duration, poor sleep quality,...     

Expression pattern of gastrointestinal markers in native colorectal epithelium, lesions, and carcinomas

Three small peptides with a typical cysteine-rich domain (TFF or P-domain) display a specific folding structure (trefoil); they are abundantly expressed on mucosal surfaces of normal and neoplastic gastrointestinal tissues. This epithelial location coincides with mucin secretion and, although not proven beyond doubt, this association is suggestive of their function in maintenance of surface integrity. Using normal colon epithelium, premalignant lesions and tumor samples and specific antibodies we studied expression of these peptides in colorectal carcinomas. RT PCR was performed to extend the sensitivity of the assays. While coexpression of pS2, hITF, MUC1 and MUC2 was demonstrated, MUC5 was absent and no simultaneous activity of pS2 and SML1 (as in gastric mucosa and carcinoma) was noted in rectal tumors. Actively transcribed and expressed cytokeratin 20 and GAPDH were used as experimental controls for immunostaining and RT-PCR, respectively.     

Mucosal immune response development: breastfeeding and environmental influence

A review of the current knowledge of mucosal immune response development indicates that migration of immunocytes to mucosal surfaces is an early event during fetal life. The morphologic development of gut-associated lymphoid tissues (lymphoid follicles, Peyer's patches and tonsils) occurs from 11-20 weeks' gestation upwards. But they are active only after birth, when usually antigenic challenge takes place. The complete development of secretory immunity is a postnatal achievement. In infancy, some environmental factors such as feeding and oral antigenic challenge seems to modulate immune response development. Breastfeeding, by means of antiinfectious, antiinflammatory and immunomodulating properties, besides completing infant secretory immunity, also stimulates immunological maturation on mucosal surfaces.     

The nursing profession in the 21st century

The present article presents the sociological analysis of the nursing profession, focussing the specificities of the profession on the basis of the component elements of a profession, according to the theoretical system of the sociology of professions. At the end of the 20th century and the beginning of the new millennium, nursing faces crucial questions for the profession, which bring back the need to restructure the strategic considerations that make up the political agenda of the nursing profession. Specific knowledge, professional qualification, particularities of the work process, monopoly of the professional exercise, and the configuration of the hierarchy of the nursing team are some of the items dealt within this article. As one of the essential professions in the health area, nursing needs to reach the next century with a new perspective, knowing how and in which conditions it will develop in a context of paradigmatic changes. Considering this new context, a political agenda for nursing professionals will have to contemplate the several aspects that make up a profession, that is, specific knowledge, exclusive labor market, form of organization, among others.     

Tobacco smoking among Portuguese high-school students.

The aim of this study was to evaluate the prevalence, behavioural patterns, and determinants of smoking among a large sample of high-school students from Porto, the second largest city in Portugal, information on sociodemographic characteristics and personal history of tobacco, alcohol, coffee, and illicit drug use was obtained from 2974 students, aged 12-19 years (48.7% female, 51.3% male), using an anonymous self-administered questionnaire. Crude and adjusted odds ratios (OR) were calculated by logistic regression analysis to estimate the association between smoking and the characteristics evaluated. Overall, 35.8% students had never smoked, 39.4% had tried it ("experimental" smokers) but were not smokers, 3.3% were former smokers, 6.6% occasional smokers, and 14.9% regular smokers. The mean age for starting smoking was 13.4 +/- 2.1 years for males and 13.4 +/- 1.6 years for females. The prevalence of current smoking was higher among males than females, but the difference was not significant. Male students were significantly more likely to smoke more cigarettes per day than were females. The prevalence of smoking was significantly associated with the following variables: being aged > 12 years; having parents who had attended school for < 4 years; having a mother (OR = 1.88), siblings (OR = 1.96) or friends (OR = 1.75) who smoked; low academic performance (OR = 1.74 for one or two failures and OR = 2.27 for more than two failures at school); and consumption of coffee (OR = 2.90), alcohol (OR = 3.53), or illicit drugs (OR = 6.69). The prevalence of smoking among adolescents increased with age. There is therefore a need for school-based tobacco prevention programmes which also deal with family influences on smoking.